HDAC8_HUMAN
ID HDAC8_HUMAN Reviewed; 377 AA.
AC Q9BY41; A6ND12; A6ND61; A6NET3; A6NJR3; A8MQ62; B4DKN0; B4DV22; Q86VC8;
AC Q9NP76; Q9NYH4;
DT 11-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 11-APR-2003, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Histone deacetylase 8 {ECO:0000303|PubMed:10748112, ECO:0000303|PubMed:10926844};
DE Short=HD8;
DE EC=3.5.1.98 {ECO:0000269|PubMed:10748112, ECO:0000269|PubMed:10922473, ECO:0000269|PubMed:10926844};
DE AltName: Full=Protein deacetylase HDAC8;
DE EC=3.5.1.- {ECO:0000269|PubMed:22885700};
DE AltName: Full=Protein decrotonylase HDAC8 {ECO:0000305};
DE EC=3.5.1.- {ECO:0000269|PubMed:28497810};
GN Name=HDAC8 {ECO:0000303|PubMed:10926844, ECO:0000312|HGNC:HGNC:13315};
GN Synonyms=HDACL1; ORFNames=CDA07;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Kidney;
RX PubMed=10748112; DOI=10.1074/jbc.m908988199;
RA Hu E., Chen Z., Fredrickson T., Zhu Y., Kirkpatrick R., Zhang G.-F.,
RA Johanson K., Sung C.-M., Liu R., Winkler J.;
RT "Cloning and characterization of a novel human class I histone deacetylase
RT that functions as a transcription repressor.";
RL J. Biol. Chem. 275:15254-15264(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION,
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF 142-HIS-HIS-143.
RC TISSUE=Uterus;
RX PubMed=10926844; DOI=10.1042/bj3500199;
RA Buggy J.J., Sideris M.L., Mak P., Lorimer D.D., McIntosh B., Clark J.M.;
RT "Cloning and characterization of a novel human histone deacetylase,
RT HDAC8.";
RL Biochem. J. 350:199-205(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Heart;
RX PubMed=10922473; DOI=10.1016/s0014-5793(00)01813-5;
RA Van den Wyngaert I., de Vries W., Kremer A., Neefs J.-M., Verhasselt P.,
RA Luyten W.H.M.L., Kass S.U.;
RT "Cloning and characterization of human histone deacetylase 8.";
RL FEBS Lett. 478:77-83(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 8).
RX PubMed=8889548; DOI=10.1101/gr.6.9.791;
RA Bonaldo M.F., Lennon G., Soares M.B.;
RT "Normalization and subtraction: two approaches to facilitate gene
RT discovery.";
RL Genome Res. 6:791-806(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5).
RC TISSUE=Colon, and Small intestine;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-247 (ISOFORM 1).
RX PubMed=10756090; DOI=10.1006/geno.2000.6128;
RA McDonell N., Ramser J., Francis F., Vinet M.-C., Rider S., Sudbrak R.,
RA Riesselman L., Yaspo M.-L., Reinhardt R., Monaco A.P., Ross F., Kahn A.,
RA Kearney L., Buckle V., Chelly J.;
RT "Characterization of a highly complex region in Xq13 and mapping of three
RT isodicentric breakpoints associated with preleukemia.";
RL Genomics 64:221-229(2000).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-146 (ISOFORM 1).
RC TISSUE=Pheochromocytoma;
RA Li Y., Huang Q., Peng Y., Song H., Yu Y., Xu S., Ren S., Chen Z., Han Z.;
RT "A novel gene expressed in human pheochromocytoma.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP INTERACTION WITH CBFA2T3.
RX PubMed=11533236; DOI=10.1128/mcb.21.19.6470-6483.2001;
RA Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N.,
RA Downing J.R., Meyers S., Hiebert S.W.;
RT "ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with
RT multiple histone deacetylases and binds mSin3A through its oligomerization
RT domain.";
RL Mol. Cell. Biol. 21:6470-6483(2001).
RN [11]
RP INTERACTION WITH PEPB2-MYH11 FUSION PROTEIN.
RX PubMed=12509458; DOI=10.1128/mcb.23.2.607-619.2003;
RA Durst K.L., Lutterbach B., Kummalue T., Friedman A.D., Hiebert S.W.;
RT "The inv(16) fusion protein associates with corepressors via a smooth
RT muscle myosin heavy-chain domain.";
RL Mol. Cell. Biol. 23:607-619(2003).
RN [12]
RP PHOSPHORYLATION BY PKA, MUTAGENESIS OF SER-39, FUNCTION, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=14701748; DOI=10.1128/mcb.24.2.765-773.2004;
RA Lee H., Rezai-Zadeh N., Seto E.;
RT "Negative regulation of histone deacetylase 8 activity by cyclic AMP-
RT dependent protein kinase A.";
RL Mol. Cell. Biol. 24:765-773(2004).
RN [13]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=15772115; DOI=10.1096/fj.04-2303fje;
RA Waltregny D., Glenisson W., Tran S.L., North B.J., Verdin E., Colige A.,
RA Castronovo V.;
RT "Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is
RT essential for smooth muscle cell contractility.";
RL FASEB J. 19:966-968(2005).
RN [14]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=16538051; DOI=10.1097/01.pas.0000188029.63706.31;
RA de Leval L., Waltregny D., Boniver J., Young R.H., Castronovo V., Oliva E.;
RT "Use of histone deacetylase 8 (HDAC8), a new marker of smooth muscle
RT differentiation, in the classification of mesenchymal tumors of the
RT uterus.";
RL Am. J. Surg. Pathol. 30:319-327(2006).
RN [15]
RP INTERACTION WITH SMG5.
RX PubMed=16809764; DOI=10.1128/mcb.01971-05;
RA Lee H., Sengupta N., Villagra A., Rezai-Zadeh N., Seto E.;
RT "Histone deacetylase 8 safeguards the human ever-shorter telomeres 1B
RT (hEST1B) protein from ubiquitin-mediated degradation.";
RL Mol. Cell. Biol. 26:5259-5269(2006).
RN [16]
RP INVOLVEMENT IN CDLS5.
RX PubMed=22889856; DOI=10.1136/jmedgenet-2012-100921;
RA Harakalova M., van den Boogaard M.J., Sinke R., van Lieshout S.,
RA van Tuil M.C., Duran K., Renkens I., Terhal P.A., de Kovel C., Nijman I.J.,
RA van Haelst M., Knoers N.V., van Haaften G., Kloosterman W., Hennekam R.C.,
RA Cuppen E., Ploos van Amstel H.K.;
RT "X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-
RT linked intellectual disability, truncal obesity, gynaecomastia,
RT hypogonadism and unusual face.";
RL J. Med. Genet. 49:539-543(2012).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, AND VARIANTS CDLS5 ARG-180; MET-311; ARG-320
RP AND ARG-334.
RX PubMed=22885700; DOI=10.1038/nature11316;
RA Deardorff M.A., Bando M., Nakato R., Watrin E., Itoh T., Minamino M.,
RA Saitoh K., Komata M., Katou Y., Clark D., Cole K.E., De Baere E.,
RA Decroos C., Di Donato N., Ernst S., Francey L.J., Gyftodimou Y.,
RA Hirashima K., Hullings M., Ishikawa Y., Jaulin C., Kaur M., Kiyono T.,
RA Lombardi P.M., Magnaghi-Jaulin L., Mortier G.R., Nozaki N., Petersen M.B.,
RA Seimiya H., Siu V.M., Suzuki Y., Takagaki K., Wilde J.J., Willems P.J.,
RA Prigent C., Gillessen-Kaesbach G., Christianson D.W., Kaiser F.J.,
RA Jackson L.G., Hirota T., Krantz I.D., Shirahige K.;
RT "HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin
RT acetylation cycle.";
RL Nature 489:313-317(2012).
RN [18]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=28497810; DOI=10.1038/cr.2017.68;
RA Wei W., Liu X., Chen J., Gao S., Lu L., Zhang H., Ding G., Wang Z.,
RA Chen Z., Shi T., Li J., Yu J., Wong J.;
RT "Class I histone deacetylases are major histone decrotonylases: evidence
RT for critical and broad function of histone crotonylation in
RT transcription.";
RL Cell Res. 27:898-915(2017).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEXES WITH TSA; SAHA; MS-344;
RP CRA-A AND DIVALENT METAL CATION, COFACTOR, ACTIVITY REGULATION, AND
RP PHOSPHORYLATION AT SER-39.
RX PubMed=15242608; DOI=10.1016/j.str.2004.04.012;
RA Somoza J.R., Skene R.J., Katz B.A., Mol C., Ho J.D., Jennings A.J.,
RA Luong C., Arvai A., Buggy J.J., Chi E., Tang J., Sang B.-C., Verner E.,
RA Wynands R., Leahy E.M., Dougan D.R., Snell G., Navre M., Knuth M.W.,
RA Swanson R.V., McRee D.E., Tari L.W.;
RT "Structural snapshots of human HDAC8 provide insights into the class I
RT histone deacetylases.";
RL Structure 12:1325-1334(2004).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH DIVALENT METAL
RP CATION, AND MUTAGENESIS OF ASP-101 AND TYR-306.
RX PubMed=17721440; DOI=10.1038/sj.embor.7401047;
RA Vannini A., Volpari C., Gallinari P., Jones P., Mattu M., Carfi A.,
RA De Francesco R., Steinkuehler C., Di Marco S.;
RT "Substrate binding to histone deacetylases as shown by the crystal
RT structure of the HDAC8-substrate complex.";
RL EMBO Rep. 8:879-884(2007).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) IN COMPLEXES WITH PEPTIDE SUBSTRATE;
RP SAHA; TSA; M-344 AND APHA, ACTIVE SITE, AND MUTAGENESIS OF ASP-101 AND
RP HIS-143.
RX PubMed=19053282; DOI=10.1021/bi801610c;
RA Dowling D.P., Gantt S.L., Gattis S.G., Fierke C.A., Christianson D.W.;
RT "Structural studies of human histone deacetylase 8 and its site-specific
RT variants complexed with substrate and inhibitors.";
RL Biochemistry 47:13554-13563(2008).
CC -!- FUNCTION: Histone deacetylase that catalyzes the deacetylation of
CC lysine residues on the N-terminal part of the core histones (H2A, H2B,
CC H3 and H4) (PubMed:10748112, PubMed:10922473, PubMed:10926844,
CC PubMed:14701748, PubMed:28497810). Histone deacetylation gives a tag
CC for epigenetic repression and plays an important role in
CC transcriptional regulation, cell cycle progression and developmental
CC events (PubMed:10748112, PubMed:10922473, PubMed:10926844,
CC PubMed:14701748). Histone deacetylases act via the formation of large
CC multiprotein complexes (PubMed:10748112, PubMed:10922473,
CC PubMed:10926844, PubMed:14701748). Also involved in the deacetylation
CC of cohesin complex protein SMC3 regulating release of cohesin complexes
CC from chromatin (PubMed:22885700). May play a role in smooth muscle cell
CC contractility (PubMed:15772115). In addition to protein deacetylase
CC activity, also has protein-lysine deacylase activity: acts as a protein
CC decrotonylase by mediating decrotonylation ((2E)-butenoyl) of histones
CC (PubMed:28497810). {ECO:0000269|PubMed:10748112,
CC ECO:0000269|PubMed:10922473, ECO:0000269|PubMed:10926844,
CC ECO:0000269|PubMed:14701748, ECO:0000269|PubMed:15772115,
CC ECO:0000269|PubMed:22885700, ECO:0000269|PubMed:28497810}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-acetyl-L-lysyl-[histone] = acetate + L-lysyl-
CC [histone]; Xref=Rhea:RHEA:58196, Rhea:RHEA-COMP:9845, Rhea:RHEA-
CC COMP:11338, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:61930; EC=3.5.1.98;
CC Evidence={ECO:0000269|PubMed:10748112, ECO:0000269|PubMed:10922473,
CC ECO:0000269|PubMed:10926844, ECO:0000269|PubMed:28497810};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58197;
CC Evidence={ECO:0000269|PubMed:10748112, ECO:0000269|PubMed:10922473,
CC ECO:0000269|PubMed:10926844, ECO:0000269|PubMed:28497810};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] = acetate + L-lysyl-
CC [protein]; Xref=Rhea:RHEA:58108, Rhea:RHEA-COMP:9752, Rhea:RHEA-
CC COMP:10731, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:61930; Evidence={ECO:0000305|PubMed:22885700};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58109;
CC Evidence={ECO:0000305|PubMed:22885700};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-(2E)-butenoyl-L-lysyl-[protein] = (2E)-2-butenoate
CC + L-lysyl-[protein]; Xref=Rhea:RHEA:69172, Rhea:RHEA-COMP:9752,
CC Rhea:RHEA-COMP:13707, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:35899, ChEBI:CHEBI:137954;
CC Evidence={ECO:0000269|PubMed:28497810};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69173;
CC Evidence={ECO:0000269|PubMed:28497810};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000269|PubMed:15242608};
CC Note=Binds 1 divalent metal cation per subunit.
CC {ECO:0000269|PubMed:15242608};
CC -!- ACTIVITY REGULATION: Its activity is inhibited by trichostatin A (TSA),
CC suberoylanilide hydroxamic acid (SAHA), 3-(1-methyl-4-phenylacetyl-1H-
CC 2-pyrrolyl)-N-hydroxy-2-propenamide (APHA), 4-dimethylamino-N-(6-
CC hydroxycarbamoyethyl)benzamide-N-hydroxy-7-(4-
CC dimethylaminobenzoyl)aminoheptanamide (MS-344), 5-(4-methyl-
CC benzoylamino)-biphenyl-3,4'-dicarboxylic acid 3-dimethylamide 4'-
CC hydroxyamide (CRA-A) and butyrate. {ECO:0000269|PubMed:15242608}.
CC -!- SUBUNIT: Interacts with PEPB2-MYH11, a fusion protein consisting of the
CC 165 N-terminal residues of CBF-beta (PEPB2) with the tail region of
CC MYH11 produced by the inversion Inv(16)(p13q22), a translocation
CC associated with acute myeloid leukemia of M4EO subtype
CC (PubMed:12509458). The PEPB2-MYH1 fusion protein also interacts with
CC RUNX1, a well known transcriptional regulator, suggesting that the
CC interaction with HDAC8 may participate in the conversion of RUNX1 into
CC a constitutive transcriptional repressor (PubMed:12509458). Interacts
CC with CBFA2T3 (PubMed:11533236). Interacts with phosphorylated
CC SMG5/EST1B; this interaction protects SMG5 from ubiquitin-mediated
CC degradation (PubMed:16809764). Associates with alpha-SMA (smooth muscle
CC alpha-actin) (PubMed:15772115). {ECO:0000269|PubMed:11533236,
CC ECO:0000269|PubMed:12509458, ECO:0000269|PubMed:15772115,
CC ECO:0000269|PubMed:16809764}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10748112,
CC ECO:0000269|PubMed:14701748}. Chromosome {ECO:0000269|PubMed:10748112}.
CC Cytoplasm {ECO:0000269|PubMed:15772115, ECO:0000269|PubMed:16538051}.
CC Note=Excluded from the nucleoli (PubMed:10748112). Found in the
CC cytoplasm of cells showing smooth muscle differentiation
CC (PubMed:15772115, PubMed:16538051). {ECO:0000269|PubMed:10748112,
CC ECO:0000269|PubMed:15772115, ECO:0000269|PubMed:16538051}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=Q9BY41-1; Sequence=Displayed;
CC Name=4;
CC IsoId=Q9BY41-4; Sequence=VSP_043426;
CC Name=5;
CC IsoId=Q9BY41-5; Sequence=VSP_043427, VSP_007177;
CC Name=6;
CC IsoId=Q9BY41-6; Sequence=VSP_043426, VSP_046834, VSP_046835,
CC VSP_046836;
CC Name=7;
CC IsoId=Q9BY41-7; Sequence=VSP_046832, VSP_046833;
CC Name=8;
CC IsoId=Q9BY41-8; Sequence=VSP_047502;
CC -!- TISSUE SPECIFICITY: Weakly expressed in most tissues. Expressed at
CC higher level in heart, brain, kidney and pancreas and also in liver,
CC lung, placenta, prostate and kidney. {ECO:0000269|PubMed:10926844,
CC ECO:0000269|PubMed:14701748, ECO:0000269|PubMed:15772115,
CC ECO:0000269|PubMed:16538051}.
CC -!- PTM: Phosphorylated by PKA on serine 39. Phosphorylation reduces
CC deacetylase activity observed preferentially on histones H3 and H4.
CC {ECO:0000269|PubMed:14701748, ECO:0000269|PubMed:15242608}.
CC -!- DISEASE: Cornelia de Lange syndrome 5 (CDLS5) [MIM:300882]: A form of
CC Cornelia de Lange syndrome, a clinically heterogeneous developmental
CC disorder associated with malformations affecting multiple systems. It
CC is characterized by facial dysmorphisms, abnormal hands and feet,
CC growth delay, cognitive retardation, hirsutism, gastroesophageal
CC dysfunction and cardiac, ophthalmologic and genitourinary anomalies.
CC {ECO:0000269|PubMed:22885700, ECO:0000269|PubMed:22889856}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 1
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK14930.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
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DR EMBL; AF230097; AAF73076.1; -; mRNA.
DR EMBL; AF245664; AAF73428.1; -; mRNA.
DR EMBL; AJ277724; CAB90213.1; -; mRNA.
DR EMBL; BQ189619; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK296641; BAG59242.1; -; mRNA.
DR EMBL; AK300895; BAG62534.1; -; mRNA.
DR EMBL; AA376331; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AI159768; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; T99283; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF212246; AAK14930.1; ALT_SEQ; mRNA.
DR EMBL; AL133500; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX295542; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC050433; AAH50433.1; -; mRNA.
DR CCDS; CCDS14420.1; -. [Q9BY41-1]
DR CCDS; CCDS55448.1; -. [Q9BY41-6]
DR CCDS; CCDS55449.1; -. [Q9BY41-4]
DR CCDS; CCDS55450.1; -. [Q9BY41-8]
DR CCDS; CCDS55451.1; -. [Q9BY41-5]
DR CCDS; CCDS55452.1; -. [Q9BY41-7]
DR RefSeq; NP_001159890.1; NM_001166418.1. [Q9BY41-4]
DR RefSeq; NP_001159891.1; NM_001166419.1. [Q9BY41-5]
DR RefSeq; NP_001159892.1; NM_001166420.1. [Q9BY41-8]
DR RefSeq; NP_001159894.1; NM_001166422.1. [Q9BY41-7]
DR RefSeq; NP_001159920.1; NM_001166448.1. [Q9BY41-6]
DR RefSeq; NP_060956.1; NM_018486.2. [Q9BY41-1]
DR PDB; 1T64; X-ray; 1.90 A; A/B=1-377.
DR PDB; 1T67; X-ray; 2.31 A; A=1-377.
DR PDB; 1T69; X-ray; 2.91 A; A=1-377.
DR PDB; 1VKG; X-ray; 2.20 A; A/B=1-377.
DR PDB; 1W22; X-ray; 2.50 A; A/B=1-377.
DR PDB; 2V5W; X-ray; 2.00 A; A/B=1-377.
DR PDB; 2V5X; X-ray; 2.25 A; A/B=1-377.
DR PDB; 3EW8; X-ray; 1.80 A; A=1-377.
DR PDB; 3EWF; X-ray; 2.50 A; A/B/C/D=1-377.
DR PDB; 3EZP; X-ray; 2.65 A; A/B=1-377.
DR PDB; 3EZT; X-ray; 2.85 A; A/B=1-377.
DR PDB; 3F06; X-ray; 2.55 A; A/B=1-377.
DR PDB; 3F07; X-ray; 3.30 A; A/B/C=1-377.
DR PDB; 3F0R; X-ray; 2.54 A; A/B/C=1-377.
DR PDB; 3MZ3; X-ray; 3.20 A; A/B=1-377.
DR PDB; 3MZ4; X-ray; 1.84 A; A/B=1-377.
DR PDB; 3MZ6; X-ray; 2.00 A; A=1-377.
DR PDB; 3MZ7; X-ray; 1.90 A; A=1-377.
DR PDB; 3RQD; X-ray; 2.14 A; A/B=1-377.
DR PDB; 3SFF; X-ray; 2.00 A; A=1-377.
DR PDB; 3SFH; X-ray; 2.70 A; A=1-377.
DR PDB; 4QA0; X-ray; 2.24 A; A/B=1-377.
DR PDB; 4QA1; X-ray; 1.92 A; A/B/C/D=1-377.
DR PDB; 4QA2; X-ray; 2.38 A; A/B=1-377.
DR PDB; 4QA3; X-ray; 2.88 A; A/B=1-377.
DR PDB; 4QA4; X-ray; 1.98 A; A=1-377.
DR PDB; 4QA5; X-ray; 1.76 A; A/B=1-377.
DR PDB; 4QA6; X-ray; 2.05 A; A/B=1-377.
DR PDB; 4QA7; X-ray; 2.31 A; A=1-377.
DR PDB; 4RN0; X-ray; 1.76 A; A/B=1-377.
DR PDB; 4RN1; X-ray; 2.18 A; A/B=1-377.
DR PDB; 4RN2; X-ray; 2.39 A; A/B=1-377.
DR PDB; 5BWZ; X-ray; 1.59 A; A/B=1-377.
DR PDB; 5D1B; X-ray; 2.90 A; A/B=1-377.
DR PDB; 5D1C; X-ray; 1.42 A; A/B=1-377.
DR PDB; 5D1D; X-ray; 2.01 A; A/B=1-377.
DR PDB; 5DC5; X-ray; 1.94 A; A/B=1-377.
DR PDB; 5DC6; X-ray; 1.55 A; A/B=1-377.
DR PDB; 5DC7; X-ray; 2.30 A; A/B=1-377.
DR PDB; 5DC8; X-ray; 1.30 A; A/B=1-377.
DR PDB; 5FCW; X-ray; 1.98 A; A/B=1-377.
DR PDB; 5THS; X-ray; 1.90 A; A/B=1-377.
DR PDB; 5THT; X-ray; 2.41 A; A/B/C/D=1-377.
DR PDB; 5THU; X-ray; 1.95 A; A/B=1-377.
DR PDB; 5THV; X-ray; 1.87 A; A/B=1-377.
DR PDB; 5VI6; X-ray; 1.24 A; A=8-377.
DR PDB; 6HSK; X-ray; 2.10 A; A/B=1-377.
DR PDB; 6ODA; X-ray; 2.88 A; A/B/C=1-377.
DR PDB; 6ODB; X-ray; 2.70 A; A/B/C=1-377.
DR PDB; 6ODC; X-ray; 2.80 A; A/B/C=1-377.
DR PDB; 7JVU; X-ray; 1.50 A; A/B=1-377.
DR PDB; 7JVV; X-ray; 1.84 A; A/B=1-377.
DR PDB; 7JVW; X-ray; 2.40 A; A/B=1-377.
DR PDBsum; 1T64; -.
DR PDBsum; 1T67; -.
DR PDBsum; 1T69; -.
DR PDBsum; 1VKG; -.
DR PDBsum; 1W22; -.
DR PDBsum; 2V5W; -.
DR PDBsum; 2V5X; -.
DR PDBsum; 3EW8; -.
DR PDBsum; 3EWF; -.
DR PDBsum; 3EZP; -.
DR PDBsum; 3EZT; -.
DR PDBsum; 3F06; -.
DR PDBsum; 3F07; -.
DR PDBsum; 3F0R; -.
DR PDBsum; 3MZ3; -.
DR PDBsum; 3MZ4; -.
DR PDBsum; 3MZ6; -.
DR PDBsum; 3MZ7; -.
DR PDBsum; 3RQD; -.
DR PDBsum; 3SFF; -.
DR PDBsum; 3SFH; -.
DR PDBsum; 4QA0; -.
DR PDBsum; 4QA1; -.
DR PDBsum; 4QA2; -.
DR PDBsum; 4QA3; -.
DR PDBsum; 4QA4; -.
DR PDBsum; 4QA5; -.
DR PDBsum; 4QA6; -.
DR PDBsum; 4QA7; -.
DR PDBsum; 4RN0; -.
DR PDBsum; 4RN1; -.
DR PDBsum; 4RN2; -.
DR PDBsum; 5BWZ; -.
DR PDBsum; 5D1B; -.
DR PDBsum; 5D1C; -.
DR PDBsum; 5D1D; -.
DR PDBsum; 5DC5; -.
DR PDBsum; 5DC6; -.
DR PDBsum; 5DC7; -.
DR PDBsum; 5DC8; -.
DR PDBsum; 5FCW; -.
DR PDBsum; 5THS; -.
DR PDBsum; 5THT; -.
DR PDBsum; 5THU; -.
DR PDBsum; 5THV; -.
DR PDBsum; 5VI6; -.
DR PDBsum; 6HSK; -.
DR PDBsum; 6ODA; -.
DR PDBsum; 6ODB; -.
DR PDBsum; 6ODC; -.
DR PDBsum; 7JVU; -.
DR PDBsum; 7JVV; -.
DR PDBsum; 7JVW; -.
DR AlphaFoldDB; Q9BY41; -.
DR SMR; Q9BY41; -.
DR BioGRID; 120968; 64.
DR ELM; Q9BY41; -.
DR IntAct; Q9BY41; 19.
DR MINT; Q9BY41; -.
DR STRING; 9606.ENSP00000362674; -.
DR BindingDB; Q9BY41; -.
DR ChEMBL; CHEMBL3192; -.
DR DrugBank; DB07350; (2E)-N-hydroxy-3-[1-methyl-4-(phenylacetyl)-1H-pyrrol-2-yl]prop-2-enamide.
DR DrugBank; DB02565; 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide.
DR DrugBank; DB07586; 5-(4-METHYL-BENZOYLAMINO)-BIPHENYL-3,4'-DICARBOXYLIC ACID 3-DIMETHYLAMIDE-4'-HYDROXYAMIDE.
DR DrugBank; DB05015; Belinostat.
DR DrugBank; DB08168; Coumarin 120.
DR DrugBank; DB14490; Ferrous ascorbate.
DR DrugBank; DB14491; Ferrous fumarate.
DR DrugBank; DB14488; Ferrous gluconate.
DR DrugBank; DB14501; Ferrous glycine sulfate.
DR DrugBank; DB14489; Ferrous succinate.
DR DrugBank; DB01592; Iron.
DR DrugBank; DB02917; N-Hydroxy-4-(Methyl{[5-(2-Pyridinyl)-2-Thienyl]Sulfonyl}Amino)Benzamide.
DR DrugBank; DB06603; Panobinostat.
DR DrugBank; DB04297; Trichostatin A.
DR DrugBank; DB02546; Vorinostat.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR DrugCentral; Q9BY41; -.
DR GuidetoPHARMACOLOGY; 2619; -.
DR GlyGen; Q9BY41; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BY41; -.
DR PhosphoSitePlus; Q9BY41; -.
DR BioMuta; HDAC8; -.
DR DMDM; 29839394; -.
DR EPD; Q9BY41; -.
DR jPOST; Q9BY41; -.
DR MassIVE; Q9BY41; -.
DR MaxQB; Q9BY41; -.
DR PaxDb; Q9BY41; -.
DR PeptideAtlas; Q9BY41; -.
DR PRIDE; Q9BY41; -.
DR ProteomicsDB; 1349; -.
DR ProteomicsDB; 79574; -. [Q9BY41-1]
DR ProteomicsDB; 79577; -. [Q9BY41-4]
DR ProteomicsDB; 79578; -. [Q9BY41-5]
DR ProteomicsDB; 875; -.
DR ProteomicsDB; 884; -.
DR Antibodypedia; 13705; 718 antibodies from 44 providers.
DR DNASU; 55869; -.
DR Ensembl; ENST00000373554.6; ENSP00000362655.1; ENSG00000147099.21. [Q9BY41-8]
DR Ensembl; ENST00000373556.8; ENSP00000362657.3; ENSG00000147099.21. [Q9BY41-7]
DR Ensembl; ENST00000373559.8; ENSP00000362660.4; ENSG00000147099.21. [Q9BY41-6]
DR Ensembl; ENST00000373573.9; ENSP00000362674.3; ENSG00000147099.21. [Q9BY41-1]
DR Ensembl; ENST00000373589.9; ENSP00000362691.4; ENSG00000147099.21. [Q9BY41-4]
DR Ensembl; ENST00000439122.7; ENSP00000414486.2; ENSG00000147099.21. [Q9BY41-5]
DR Ensembl; ENST00000649116.1; ENSP00000497925.1; ENSG00000147099.21. [Q9BY41-8]
DR GeneID; 55869; -.
DR KEGG; hsa:55869; -.
DR MANE-Select; ENST00000373573.9; ENSP00000362674.3; NM_018486.3; NP_060956.1.
DR UCSC; uc004eau.3; human. [Q9BY41-1]
DR CTD; 55869; -.
DR DisGeNET; 55869; -.
DR GeneCards; HDAC8; -.
DR GeneReviews; HDAC8; -.
DR HGNC; HGNC:13315; HDAC8.
DR HPA; ENSG00000147099; Low tissue specificity.
DR MalaCards; HDAC8; -.
DR MIM; 300269; gene.
DR MIM; 300882; phenotype.
DR neXtProt; NX_Q9BY41; -.
DR OpenTargets; ENSG00000147099; -.
DR Orphanet; 199; Cornelia de Lange syndrome.
DR Orphanet; 3459; Wilson-Turner syndrome.
DR PharmGKB; PA37766; -.
DR VEuPathDB; HostDB:ENSG00000147099; -.
DR eggNOG; KOG1342; Eukaryota.
DR GeneTree; ENSGT00940000157843; -.
DR HOGENOM; CLU_007727_7_6_1; -.
DR InParanoid; Q9BY41; -.
DR OMA; CFWHSTG; -.
DR OrthoDB; 732770at2759; -.
DR PhylomeDB; Q9BY41; -.
DR TreeFam; TF106175; -.
DR BRENDA; 3.5.1.98; 2681.
DR PathwayCommons; Q9BY41; -.
DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-2467813; Separation of Sister Chromatids. [Q9BY41-1]
DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion. [Q9BY41-1]
DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR Reactome; R-HSA-3214815; HDACs deacetylate histones.
DR Reactome; R-HSA-350054; Notch-HLH transcription pathway.
DR SABIO-RK; Q9BY41; -.
DR SignaLink; Q9BY41; -.
DR SIGNOR; Q9BY41; -.
DR BioGRID-ORCS; 55869; 37 hits in 723 CRISPR screens.
DR ChiTaRS; HDAC8; human.
DR EvolutionaryTrace; Q9BY41; -.
DR GeneWiki; HDAC8; -.
DR GenomeRNAi; 55869; -.
DR Pharos; Q9BY41; Tclin.
DR PRO; PR:Q9BY41; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9BY41; protein.
DR Bgee; ENSG00000147099; Expressed in colonic epithelium and 172 other tissues.
DR ExpressionAtlas; Q9BY41; baseline and differential.
DR Genevisible; Q9BY41; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR GO; GO:0000118; C:histone deacetylase complex; IBA:GO_Central.
DR GO; GO:0000228; C:nuclear chromosome; TAS:ProtInc.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; TAS:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; TAS:UniProtKB.
DR GO; GO:0004407; F:histone deacetylase activity; IDA:UniProtKB.
DR GO; GO:0160009; F:histone decrotonylase activity; IDA:UniProtKB.
DR GO; GO:0030544; F:Hsp70 protein binding; IPI:BHF-UCL.
DR GO; GO:0051879; F:Hsp90 protein binding; IPI:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; TAS:UniProtKB.
DR GO; GO:0016575; P:histone deacetylation; IEA:InterPro.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; TAS:ProtInc.
DR GO; GO:0071922; P:regulation of cohesin loading; IMP:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IDA:BHF-UCL.
DR GO; GO:0032204; P:regulation of telomere maintenance; IMP:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007062; P:sister chromatid cohesion; IMP:UniProtKB.
DR Gene3D; 3.40.800.20; -; 1.
DR InterPro; IPR000286; His_deacetylse.
DR InterPro; IPR003084; His_deacetylse_1.
DR InterPro; IPR023801; His_deacetylse_dom.
DR InterPro; IPR037138; His_deacetylse_dom_sf.
DR InterPro; IPR023696; Ureohydrolase_dom_sf.
DR Pfam; PF00850; Hist_deacetyl; 1.
DR PIRSF; PIRSF037913; His_deacetylse_1; 1.
DR PRINTS; PR01270; HDASUPER.
DR PRINTS; PR01271; HISDACETLASE.
DR SUPFAM; SSF52768; SSF52768; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromatin regulator; Chromosome;
KW Cytoplasm; Disease variant; Hydrolase; Intellectual disability;
KW Metal-binding; Nucleus; Obesity; Phosphoprotein; Reference proteome;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..377
FT /note="Histone deacetylase 8"
FT /id="PRO_0000114708"
FT REGION 14..324
FT /note="Histone deacetylase"
FT ACT_SITE 143
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:19053282"
FT BINDING 101
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19053282"
FT BINDING 151
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19053282"
FT BINDING 178
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:17721440"
FT BINDING 180
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:17721440"
FT BINDING 267
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:17721440"
FT BINDING 306
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19053282"
FT MOD_RES 39
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15242608"
FT VAR_SEQ 56..146
FT /note="Missing (in isoform 4 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043426"
FT VAR_SEQ 147..377
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:8889548"
FT /id="VSP_047502"
FT VAR_SEQ 147..158
FT /note="DEASGFCYLNDA -> ETCVYVALYKAF (in isoform 7)"
FT /evidence="ECO:0000305"
FT /id="VSP_046832"
FT VAR_SEQ 159..377
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000305"
FT /id="VSP_046833"
FT VAR_SEQ 185..210
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_046834"
FT VAR_SEQ 246..272
FT /note="SVLKEVYQAFNPKAVVLQLGADTIAGD -> RYEPPAPNPGL (in
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043427"
FT VAR_SEQ 246..256
FT /note="SVLKEVYQAFN -> RYEPPAPNPGL (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_046835"
FT VAR_SEQ 257..377
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_046836"
FT VAR_SEQ 273..377
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_007177"
FT VARIANT 180
FT /note="H -> R (in CDLS5; dbSNP:rs397515416)"
FT /evidence="ECO:0000269|PubMed:22885700"
FT /id="VAR_069140"
FT VARIANT 311
FT /note="T -> M (in CDLS5; dbSNP:rs397515417)"
FT /evidence="ECO:0000269|PubMed:22885700"
FT /id="VAR_069141"
FT VARIANT 320
FT /note="G -> R (in CDLS5; dbSNP:rs398122909)"
FT /evidence="ECO:0000269|PubMed:22885700"
FT /id="VAR_069142"
FT VARIANT 334
FT /note="H -> R (in CDLS5; dbSNP:rs397515418)"
FT /evidence="ECO:0000269|PubMed:22885700"
FT /id="VAR_069143"
FT MUTAGEN 39
FT /note="S->A: Enhances the deacetylase activity."
FT /evidence="ECO:0000269|PubMed:14701748"
FT MUTAGEN 39
FT /note="S->E: Decreases the deacetylase activity."
FT /evidence="ECO:0000269|PubMed:14701748"
FT MUTAGEN 101
FT /note="D->A: Complete loss of catalytical activity.
FT Complete loss of catalytical activity; when associated with
FT F-306."
FT /evidence="ECO:0000269|PubMed:17721440,
FT ECO:0000269|PubMed:19053282"
FT MUTAGEN 101
FT /note="D->E: Partial loss of catalytical activity."
FT /evidence="ECO:0000269|PubMed:17721440,
FT ECO:0000269|PubMed:19053282"
FT MUTAGEN 101
FT /note="D->L: Complete loss of catalytical activity."
FT /evidence="ECO:0000269|PubMed:17721440,
FT ECO:0000269|PubMed:19053282"
FT MUTAGEN 101
FT /note="D->N: Almost complete loss of catalytical activity."
FT /evidence="ECO:0000269|PubMed:17721440,
FT ECO:0000269|PubMed:19053282"
FT MUTAGEN 142..143
FT /note="HH->AA: Strongly reduces histone deacetylase
FT activity."
FT /evidence="ECO:0000269|PubMed:10926844"
FT MUTAGEN 143
FT /note="H->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:19053282"
FT MUTAGEN 306
FT /note="Y->F: Loss of catalytic activity. Complete loss of
FT catalytic activity; when associated with A-101."
FT /evidence="ECO:0000269|PubMed:17721440"
FT CONFLICT 31
FT /note="L -> P (in Ref. 7; AAH50433)"
FT /evidence="ECO:0000305"
FT CONFLICT 179
FT /note="L -> V (in Ref. 8; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="R -> W (in Ref. 2; AAF73428)"
FT /evidence="ECO:0000305"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:5VI6"
FT HELIX 22..28
FT /evidence="ECO:0007829|PDB:5VI6"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:4RN0"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:3EZP"
FT HELIX 37..47
FT /evidence="ECO:0007829|PDB:5VI6"
FT HELIX 50..53
FT /evidence="ECO:0007829|PDB:5VI6"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:5VI6"
FT HELIX 64..67
FT /evidence="ECO:0007829|PDB:5VI6"
FT TURN 68..70
FT /evidence="ECO:0007829|PDB:5VI6"
FT HELIX 73..84
FT /evidence="ECO:0007829|PDB:5VI6"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:3F0R"
FT TURN 91..97
FT /evidence="ECO:0007829|PDB:5DC8"
FT STRAND 99..102
FT /evidence="ECO:0007829|PDB:5VI6"
FT HELIX 108..127
FT /evidence="ECO:0007829|PDB:5VI6"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:1W22"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:5VI6"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:5VI6"
FT HELIX 157..165
FT /evidence="ECO:0007829|PDB:5VI6"
FT TURN 166..168
FT /evidence="ECO:0007829|PDB:5VI6"
FT STRAND 172..176
FT /evidence="ECO:0007829|PDB:5VI6"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:5VI6"
FT HELIX 183..188
FT /evidence="ECO:0007829|PDB:5VI6"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:5VI6"
FT STRAND 193..202
FT /evidence="ECO:0007829|PDB:5VI6"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:1VKG"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:5VI6"
FT STRAND 225..231
FT /evidence="ECO:0007829|PDB:5VI6"
FT HELIX 237..255
FT /evidence="ECO:0007829|PDB:5VI6"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:5VI6"
FT HELIX 266..268
FT /evidence="ECO:0007829|PDB:5VI6"
FT HELIX 281..292
FT /evidence="ECO:0007829|PDB:5VI6"
FT STRAND 297..301
FT /evidence="ECO:0007829|PDB:5VI6"
FT HELIX 308..323
FT /evidence="ECO:0007829|PDB:5VI6"
FT HELIX 337..340
FT /evidence="ECO:0007829|PDB:5VI6"
FT TURN 341..343
FT /evidence="ECO:0007829|PDB:5VI6"
FT HELIX 359..372
FT /evidence="ECO:0007829|PDB:5VI6"
FT TURN 374..376
FT /evidence="ECO:0007829|PDB:5D1C"
SQ SEQUENCE 377 AA; 41758 MW; CAA1B91894FB5013 CRC64;
MEEPEEPADS GQSLVPVYIY SPEYVSMCDS LAKIPKRASM VHSLIEAYAL HKQMRIVKPK
VASMEEMATF HTDAYLQHLQ KVSQEGDDDH PDSIEYGLGY DCPATEGIFD YAAAIGGATI
TAAQCLIDGM CKVAINWSGG WHHAKKDEAS GFCYLNDAVL GILRLRRKFE RILYVDLDLH
HGDGVEDAFS FTSKVMTVSL HKFSPGFFPG TGDVSDVGLG KGRYYSVNVP IQDGIQDEKY
YQICESVLKE VYQAFNPKAV VLQLGADTIA GDPMCSFNMT PVGIGKCLKY ILQWQLATLI
LGGGGYNLAN TARCWTYLTG VILGKTLSSE IPDHEFFTAY GPDYVLEITP SCRPDRNEPH
RIQQILNYIK GNLKHVV
